Postoperative analgesia is usually inadequate, perhaps because conventional approaches to pain relief do not take account of underlying mechanisms. Pre-emptive analgesia may prevent nociceptive inputs generated during surgery from sensitising central neurons and, therefore, may reduce postoperative pain. In a randomised, double-blind study, we compared the effect of parenteral morphine when given before or after total abdominal hysterectomy in 60 patients. 10 mg of morphine were given intramuscularly 1 hour before operation (im pre), intravenously at induction of anaesthesia (iv pre), or intravenously at closure of the peritoneum (iv post). Response was assessed by morphine consumption from patient-controlled analgesia machines which was found to be significantly reduced in the iv pre group for 24 hours after operation compared with the iv post group. Pain sensitivity around the wound was reduced in both preoperative treatment groups compared with the iv post group. We conclude that pre-emptive analgesia with intravenous morphine, by preventing the establishment of central sensitisation during surgery, reduces postoperative pain, analgesic requirements, and secondary hyperalgesia.